Design of a Tetravalent RGD Peptide Capable of Simultaneous Binding with Multiple Integrin αvβ3 for Targeted...

Area of Science:

• Nuclear medicine
• Radiopharmaceutical chemistry
• Oncology

Background:

• Targeted radionuclide therapy requires radioligands with high and sustained tumor accumulation.
• Previous work demonstrated a hexavalent RGD peptide labeled with technetium-99m (^99mTc-(RGD)₆) effectively targets integrin αvβ3 for imaging.

Purpose of the Study:

• To develop a multivalent RGD peptide labeled with astatine-211 (²¹¹At) for targeted radionuclide therapy.
• To evaluate the potential of ²¹¹At-(RGD)₄ as a therapeutic agent targeting integrin αvβ3.

Main Methods:

• Synthesis of a tetravalent RGD peptide (H₂N-(RGD)₄).
• Radiolabeling with iodine-125 (¹²⁵I) for initial studies, followed by labeling with ²¹¹At.
• In vivo biodistribution studies to assess tumor uptake and retention.

Main Results:

• ¹²⁵I-(RGD)₄ demonstrated simultaneous binding to integrin αvβ3 and comparable tumor uptake to ^99mTc-(RGD)₆.
• ²¹¹At-(RGD)₄ was synthesized with >95% radiochemical purity.
• ²¹¹At-(RGD)₄ exhibited a biodistribution pattern similar to ¹²⁵I-(RGD)₄.

Conclusions:

• ²¹¹At-(RGD)₄ retains the binding capabilities of RGD peptides.
• The compound shows promising characteristics for integrin αvβ3-targeted radionuclide therapy.
• ²¹¹At-(RGD)₄ is a potential radioligand for cancer treatment.